Turnover of Adrenergic Receptors Under Normal and Desensitized Conditions

Abstract

Alpha₁ and beta adrenergic receptor metabolism was investigated by studying receptor reappearance after an irreversible blockade. Phenoxybenzamine was used to irreversibly block alpha₁ adrenergic receptors both in vitro in the BC₃H₁ cell line and in vivo in rat submaxillary glands. In these two systems, the alpha₁ adrenergic receptor reappearance followed a monoexponential kinetic allowing to determine the half-life of the receptor (23h in vitro, 33h in vivo) as well as the rate of receptor synthesis and degradation. the receptor reappearance was due to receptor synthesis since it was blocked by cycloheximide. The irreversible blockade of beta adrenergic receptors was done with an alkylating beta adrenergic antagonist that we recently developped : Br-pindolol (1). This ligand has high efficiency and blocked at 10⁻⁷ M 80-90% of the beta adrenergic receptors present in C₆ glioma cells in culture. After this irreversible blockade, receptors reappeared only during cell division. At confluency, when cells did not significantly divide, receptor synthesis could hardly be detectable. Therefore, at confluency, the metabolic stability of the beta adrenergic receptor is considerable, compared to that of the alpha₁ adrenergic receptor. This stability was confirmed by the observation that after an almost complete “down-regulation” of the beta adrenergic receptor, receptor repopulation of the C₆ glioma cells was total and occured in the presence of cycloheximide.